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CHOLESTEROL LOWERING

CHOLESTEROL LOWERING. Lipids in T1D and T2D. CHD mortality rises in line with total cholesterol. 100. Annual age-standardised CHD mortality (%). 10. 1. 3.5. 4.0. 4.5. 5.0. 5.5. 6.0. 6.5. 7.0. 7.5. 8.0. Total cholesterol (mmol/l).

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CHOLESTEROL LOWERING

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  1. CHOLESTEROL LOWERING

  2. Lipids in T1D and T2D

  3. CHD mortality rises in line with total cholesterol 100 Annual age-standardised CHD mortality (%) 10 1 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 Total cholesterol (mmol/l) Stamler J, Wentworth D, Neaton JD. JAMA 1986;256(10):2823-2828.

  4. CHD mortality rises in line with total cholesterol 100 Annual age-standardised CHD mortality (%) 10 1 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 Total cholesterol (mmol/l) Stamler J, Wentworth D, Neaton JD. JAMA 1986;256(10):2823-2828.

  5. 1.8% 1.6% 1.4% 1.2% 1.0% Annual CHD mortality rate 0.8% 0.6% 0.4% 0.2% 0.0% 4 4.5 5 5.5 6 6.5 7 7.5 Total cholesterol (mmol/l) Reducing cholesterol reduces CHD mortality 4S LIPID HPS High risk study groups CARE POSCH Low risk study groups WOSCOPS LRC AFCAPS/TexCAPS Helsinki Start of study End of study

  6. MRC/BHF Heart Protection Study • 20,000 subjects with Increased CHD risk due to prior disease : • Myocardial infarction or other CHD ; • Occlusive disease of non-coronary arteries ; or • Diabetes mellitus or treated hypertension. • Age 40-80 years • Total cholesterol >3.5 mmol/l ( >135mg/dl) • Randomised to simvastatin 40 mg or placebo

  7. CARDS Collaborative Atorvastatin Diabetes Study Helen Colhoun, John Betteridge, Paul Durrington, Graham Hitman, Andrew Neil, Shona Livingstone, Margaret Thomason, Michael Mackness, Valentine Menys, John Fuller on behalf of the CARDS Investigators

  8. Placebo 2838 patients Atorvastatin 10mg CARDS Design Placebo Primary prevention diabetes patients with one other risk factor (hypertension, smoker, micro-albuminuria, retinopathy)

  9. Event Placebo* Atorva* Hazard Ratio Risk Reduction (CI) Primary endpoint** 127 (9.0%) 83 (5.8%) 37% (17- 52) p=0.001 Acute coronary events 77 (5.5%) 51 (3.6%) 36% (9- 55) Coronary revascularisation 34 (2.4%) 24 (1.7%) 31% (16- 59) Stroke 39 (2.8%) 21 (1.5%) 48% (11- 69) ** Fatal MI, other acute CHD death, non fatal MI, unstable angina, CABG, fatal stroke, non fatal stroke .2 .4 .6 .8 1 1.2 Treatment effect on the primary endpoint

  10. Treatment effect on the primary endpoint by lipid levels .2 .4 .6 .8 1 1.2

  11. JBS 2 : indications for statin therapy in type 1 or type 2 diabetes • Age > 40 years • Retinopathy of greater than background severity • Nephropathy, including microalbuminuria • Poor glycaemic control (HbA1c > 9%) • Hypertension requiring treatment • Elevated total cholesterol ( > 6.0 mmol/l) • Metabolic syndrome • Family history of premature CHD in a first degree relative

  12. Total cholesterol still > 4 ? • Use a more potent statin ? • Add cholesterol absorption inhibitor : ezetimibe ? • Role of fibrate or nicotinic acid ?

  13. Cost Effectiveness British National Formulary 2008

  14. Patients not on target on simvastatin 40 mg

  15. Fibrates : FIELD Study • 9795 subjects with T2D : 7664 no CVD • Fenofibrate 200 mg versus placebo • Average 5 year follow up • 36% of placebo group and 19% of fenofibrate group given statins • Fenofibrate : TC  11%, LDL  12%, HDL  5% , TG  29% • Primary endpoint  11% (NS) • Reduction in laser therapy / progression of albuminuria in fenofibrate group • Myositis / rhabdomyolysis < 1% FIELD Study Investigators, Lancet 2005; 366; 1849-1861

  16. The Alphabet Strategy • Advice Smoking , diet , exercise • Blood pressure < 140/80 • Cholesterol TC < 4.0 mmol/l , LDL ≤ 2.0 mmol/l HDL > 1.0 mmol/l, TGs < 1.7 mmol/l • Diabetes control HbA1c ≤ 7% • Eye examination Annual examination • Feet examination Annual examination • Guardian drugs Aspirin, ACEI, ARB, statins

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